1. Hepatocytes were isolated by collagenase perfusion of livers from fed rats and established in stationary monolayer culture. 2. Degradation of intracellular protein was measured in these monolayers after labelling for 16h with [3H]leucine followed by a 3h chase period in medium containing 2mM-leucine. 3. Proteolysis in this system was stimulated by physiological concentrations of glucagon and...

We previously demonstrated that infusion of an intestinal peptide called xenin-25 (Xen) amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP) on insulin secretion rates (ISRs) and plasma glucagon levels in humans. However, these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes. Thus, Xen rather than GIP signaling to islets fails early during develop...

The significance of glucagon in the pathophysiology of diabetes mellitus is widely recognized, but the mechanisms underlying dysregulated glucagon secretion are still unclear. Here, we explored the molecular mechanisms of glucagon dysregulation, using an in vitro model. Hamster-derived glucagon-secreting InR1G cells were exposed to high glucose (25 mM) levels for 12 h before analyzing glucagon ...

The net hepatic metabolism of amino glycerol, lactate, and pyruvate was determined in conscious fed sheep by multiplying the venoarterial concentration differences by the hepatic blood or plasma flow. In each experiment several sets of control blood samples were taken; glucagon or insulin then was infused intraportally for 2 h during which additional samples were taken. Four types of experiment...

During the past 30 years evidence has been accumulating which suggests that glucagon (the hyperglycemic-glycogenolytic factor of the pancreas) is a true hormone and that it is produced in the Islets of Langerhans (1, 2). Its purification and crystallization were finally accomplished in 1953 by Staub, Sinn, and Behrens (3). The crystalline material is a simple protein with a molecular weight of ...

OBJECTIVE In advanced beta-cell failure, counterregulatory glucagon responses may be impaired due to a reduced decrement in insulin secretion during the development of hypoglycemia. The present studies were therefore undertaken to test the hypothesis that these may be improved by increasing this decrement in insulin secretion. RESEARCH DESIGN AND METHODS Twelve subjects with type 2 diabetes w...

Microsomal epoxide hydrolase (mEH) plays an important role in the detoxification of a broad range of epoxide intermediates and has been reported to be decreased during diabetes and fasting. The signaling pathways involved in the regulation of mEH expression in response to insulin and glucagon were examined in primary cultured rat hepatocytes. mEH protein levels were increased 2- to 6-fold in he...

Nitric oxide (NO) produced by islet constitutive NO synthase (cNOS) is a putative modulator of islet hormone secretion. We show here for the first time that the release of insulin induced byl-arginine orl-homoarginine is inhibited and that of glucagon stimulated in parallel with the rate of islet NO production. It was found thatl-homoarginine was ≈25-30% less potent thanl-arginine as an insulin...

To determine if both phases of glucagon secretion are excessive in diabetes, arginine was admimistered intravenously as pulses and as infusions to normal subjects, insulin-dependent diabetics, and noninsulin-requiring diabetics. The acute phase of glucagon secretion, in response to arginine pulses at four different doses (submaximal to maximal alpha-cell stimulating), was indistinguishable in t...

Rats were given soybean trypsin inhibitor or repeatedly injected with pancreozymin (daily 40 I.D.U./kg) for 7 days, and the insulin and glucagon contents of the pancreas were measured. The insulin and glucagon contents were markedly increased after these treatments and this effect was especially conspicuous after injections of large doses (daily 120 I.D.U.) of depot-type pancreozymin. Insulin c...